Barbiturate-induced excitation can vary over a continuous spectrum from mild preanesthetic delirium to maximal or grand mal type seizures. The intensity of excitation depends not only upon the specific barbiturate employed, but also upon the species in which it is tested and upon idiosyncratic responses of individuals within the same species. This project is predicated on the hypothesis that barbiturates possess an excitatory component of action entirely independent of general depression and that this excitatory action may be pertinent to basic characteristics of barbiturate anesthesia, idiosyncratic stimulant effects of barbiturates used as sedatives, and hyperexcitability during withdrawal from barbiturate addiction. The goal of this project is to identify the mechanisms underlying the paradoxical excitatory effects of barbiturates. The cat spinal reflex arc will be used to study the sites and possible mechanism of action of barbiturate-induced excitation in relatively intact animals. These studies will be augmented by in vitro study of isolated preparations with the object of identifying an excitatory mechanism in terms of changes in membrane premeability to specific ions. The drugs employed will include a series of barbiturates whose gross effects cover the entire spectrum of barbiturate-induced excitation from maximal seizures through mild preanesthetic excitation.